brains ampGAINS November 2 2013 912 am Center For Tomorrow httpubnjacobsneurowordpresscomhome wolfegil httpswwwfacebookcomUBMDNeurology Gil I Wolfe MD Irvin and Rosemary Smith Professor and Chair since Jan 2012 ID: 754116
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UB
Dept
of Neurology
UBMD Neurology/JNI
brains&GAINSNovember 2, 20139-12 a.m.Center For Tomorrow
http://ubnjacobsneuro.wordpress.com/home/
@
wolfegil
https://www.facebook.com/UBMDNeurologySlide2
Gil I. Wolfe, MDIrvin and Rosemary Smith Professor and Chair since Jan 20129 new Dept. of Neurology faculty3 stroke1 multiple sclerosis1 adult epilepsy
1 child neurology1 neurocritical care2 neuroimaging (100% research)Clinical and investigative career in neuromuscular medicineMyasthenia Gravis (MG) ECU-MG-301: Double-blind, placebo –controlled trial of eculizimab in refractory generalized MGClinical chair of international, NIH supported study of
thymectomy in MGPeripheral NeuropathyGBS longitudinal follow-up study (IGOS)OthersINSIGHTSIV immunoglobulin usage patterns across U.S. Slide3
Aging, Alzheimer’s Disease & MemoryKinga Szigeti, MD, PhDDirector, Memory Disorders ProgramSlide4
Disease Classification
NMJ
Muscle
Axon
Myelin
Motor
neuron
Neuronopathies
& Neuropathies
ALS, PLS, SMA,
diabetic neuropathy,
t
oxic neuropathy, GBS,
CMT
Myopathies
Muscular dystrophy,
p
olymyositis
,
d
ermatomyositis
, IBM
Neuromuscular
Junction Disorders
MG, botulismSlide5
Eculizimab in MGMonoclonal antibody that binds complement C5, preventing cleavage to C5aComplement activation is key component to damage of muscle membrane in MGCobra venom blocks complement and prevents induction of experimental autoimmune MG (EAMG)Membrane attack complex (MAC) present on muscle membrane in EAMG animals and MG patientsUp to 10% of MG patients refractorySlide6
MG and complement-mediated injury
Shiraishi et al. Ann Neurol 2005;57:289 (biceps biopsies)
Control
AChRAb
MuSKAb
MuSKAbSlide7
Phase II Study of Eculizimabn=14 (30-72 yrs)AChRAb+ and failed 2 immunosuppressives, including prednisone, for ≥ 1
yrNo IVIg for 8 weeks or plasma exchange for 12 weeksResultsReduction by >3 QMG points during eculizimab vs. placebo marginally significant (p=0.0577)Side effectsMild to moderate
Nausea, back pain, headache, pharyngitis 3 serious adverse advents on both active and placebo treatmentHoward JF et al. Muscle Nerve 2013;48:76--84
600 mg IV qwk for 4 wks
900 mg IV at 5th q2wks for 12 wksSlide8
ECU-MG-301: Eculizimab in refractory generalized MGPhase 3, randomized (1:1), double-blinded, placebo-controlled trialTreatment duration 26
wksAChRAb+, age ≥ 18 yrsMG-ADL score ≥ 6MG-ADL is the primary outcome measureQMG, MGC, QOL also measured Failed ≥2 immunotherapies for at least 1 yrNo IVIg or PE within
4 wksCan continue on current immunosuppressive treatments without dose changes